Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (666 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
An amino alcohol with a long unsaturated hydrocarbon chain. Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (Dorland, 28th ed)
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: 4-Sphingenine; 4 Sphingenine.
Where it fits in the MeSH classification
- Broader topics
- Amino Alcohols; Glycols
- Narrower topics
- Fingolimod Hydrochloride; Psychosine
- See also
- Sphingolipids
Research landscape
PubMed indexes 11,068 records tagged with the MeSH heading “Sphingosine” (counts retrieved 2026-10-31). 2,401 of them (21.7%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 4,148 records.
Reviews account for 1,352 records (12.2%) and meta-analyses for 34. Randomized controlled trials number 124 (1.1%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 1,669 |
| 2000-2009 | 2,850 |
| 2010-2019 | 4,148 |
| 2020 onward | 2,401 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 1,352 | 12.2% |
| Meta-analyses | 34 | 0.3% |
| Randomized controlled trials | 124 | 1.1% |
Method: PubMed query "Sphingosine"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
Cellular stress promotes NOD1/2-dependent inflammation via the endogenous metabolite sphingosine-1-phosphate [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Cellular stress has been associated with inflammation, yet precise underlying mechanisms remain elusive.
- Closing excerpt
- We propose S1P, an endogenous metabolite, as a novel NOD1/2 activator and NOD1/2 as molecular hubs integrating bacterial and metabolic cues.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (134 words)
Cellular stress has been associated with inflammation, yet precise underlying mechanisms remain elusive. In this study, various unrelated stress inducers were employed to screen for sensors linking altered cellular homeostasis and inflammation. We identified the intracellular pattern recognition receptors NOD1/2, which sense bacterial peptidoglycans, as general stress sensors detecting perturbations of cellular homeostasis. NOD1/2 activation upon such perturbations required generation of the endogenous metabolite sphingosine-1-phosphate (S1P). Unlike peptidoglycan sensing via the leucine-rich repeats domain, cytosolic S1P directly bound to the nucleotide binding domains of NOD1/2, triggering NF-κB activation and inflammatory responses. In sum, we unveiled a hitherto unknown role of NOD1/2 in surveillance of cellular homeostasis through sensing of the cytosolic metabolite S1P. We propose S1P, an endogenous metabolite, as a novel NOD1/2 activator and NOD1/2 as molecular hubs integrating bacterial and metabolic cues.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33942347 · DOI · PMC8246065
Sphinganine recruits TLR4 adaptors in macrophages and promotes inflammation in murine models of sepsis and melanoma [2]
Abstract reading summary — source excerpts
- Opening excerpt
- After recognizing its ligand lipopolysaccharide, Toll-like receptor 4 (TLR4) recruits adaptor proteins to the cell membrane, thereby initiating downstream signaling and triggering inflammation.
- Closing excerpt
- Therefore, sphinganine biosynthesis is required for the initiation of TLR4 signal transduction and serves as a checkpoint for macrophage pattern recognition in sepsis and melanoma mouse models.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (148 words)
After recognizing its ligand lipopolysaccharide, Toll-like receptor 4 (TLR4) recruits adaptor proteins to the cell membrane, thereby initiating downstream signaling and triggering inflammation. Whether this recruitment of adaptor proteins is dependent solely on protein-protein interactions is unknown. Here, we report that the sphingolipid sphinganine physically interacts with the adaptor proteins MyD88 and TIRAP and promotes MyD88 recruitment in macrophages. Myeloid cell-specific deficiency in serine palmitoyltransferase long chain base subunit 2, which encodes the key enzyme catalyzing sphingolipid biosynthesis, decreases the membrane recruitment of MyD88 and inhibits inflammatory responses in in vitro bone marrow-derived macrophage and in vivo sepsis models. In a melanoma mouse model, serine palmitoyltransferase long chain base subunit 2 deficiency decreases anti-tumor myeloid cell responses and increases tumor growth. Therefore, sphinganine biosynthesis is required for the initiation of TLR4 signal transduction and serves as a checkpoint for macrophage pattern recognition in sepsis and melanoma mouse models.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39025856 · DOI · PMC11258287
Alterations of lipid metabolism provide serologic biomarkers for the detection of asymptomatic versus symptomatic COVID-19 patients [3]
Abstract reading summary — source excerpts
- Opening excerpt
- COVID-19 pandemic exerts a health care emergency around the world.
- Closing excerpt
- Thus, reduced sphingosine levels provide a sensitive and selective serologic biomarker for the early identification of asymptomatic versus symptomatic COVID-19 patients.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (201 words)
COVID-19 pandemic exerts a health care emergency around the world. The illness severity is heterogeneous. It is mostly unknown why some individuals who are positive for SARS-CoV-2 antibodies stay asymptomatic while others show moderate to severe disease symptoms. Reliable biomarkers for early detection of the disease are urgently needed to attenuate the virus's spread and help make early treatment decisions. Bioactive sphingolipids play a crucial role in the regulation of viral infections and pro-inflammatory responses involved in the severity of COVID-19. However, any roles of sphingolipids in COVID-19 development or detection remain unknown. In this study, lipidomics measurement of serum sphingolipids demonstrated that reduced sphingosine levels are highly associated with the development of symptomatic COVID-19 in the majority (99.24%) SARS-CoV-2-infected patients compared to asymptomatic counterparts. The majority of asymptomatic individuals (73%) exhibited increased acid ceramidase (AC) in their serum, measured by Western blotting, consistent with elevated sphingosine levels compared to SARS-CoV-2 antibody negative controls. AC protein was also reduced in almost all of the symptomatic patients' serum, linked to reduced sphingosine levels, measured in longitudinal acute or convalescent COVID-19 samples. Thus, reduced sphingosine levels provide a sensitive and selective serologic biomarker for the early identification of asymptomatic versus symptomatic COVID-19 patients.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34244584 · DOI · PMC8270895
Cancer-Associated Fibroblast-Derived Sphingosine-1-Phosphate Activates a MALL-SDC4 Axis to Facilitate Perineural Invasion in Pancreatic Cancer [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Pancreatic ductal adenocarcinoma (PDAC) frequently exhibits perineural invasion (PNI), a clinicopathologic feature strongly associated with local recurrence and poor survival, yet lacking effective targeted interventions.
- Closing excerpt
- These findings uncover a metabolite-driven MALL-SDC4 program connecting stromal metabolism to neural invasion, and identify promising therapeutic targets for PDAC.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (183 words)
Pancreatic ductal adenocarcinoma (PDAC) frequently exhibits perineural invasion (PNI), a clinicopathologic feature strongly associated with local recurrence and poor survival, yet lacking effective targeted interventions. By integrating patient cohorts with single-cell and bulk transcriptomics, multiplex immunofluorescence, and functional assays, this study defines a stromal-tumor signaling axis facilitating neural invasion. Cancer-associated fibroblasts (CAFs), particularly a myofibroblastic CAF-enriched population, upregulate sphingosine kinase 1 (SPHK1) and increase secretion of sphingosine-1-phosphate (S1P), which activates sphingosine-1-phosphate receptor 3 (S1PR3)/JNK/JUN signaling to transcriptionally induce MAL-like protein (MALL) in cancer cells. MALL binds to syndecan-4 (SDC4) and promotes its recycling to the plasma membrane, thereby increasing surface SDC4 abundance. This MALL-SDC4 program promotes RhoA/phosphorylated myosin light chain 2 (p-MLC2)-dependent amoeboid motility and sensitizes cancer cells to Schwann cell-derived pleiotrophin, strengthening directed neural invasion. Disruption of the axis through SPHK1 knockdown in CAFs, genetic perturbation of MALL or SDC4 in cancer cells, or adeno-associated virus-mediated SPHK1 or SDC4 knockdown in KPC (KrasLSL-G12D/+; Trp53LSL-R172H/+; Pdx1-Cre) mice significantly reduces PNI and tumor burden. These findings uncover a metabolite-driven MALL-SDC4 program connecting stromal metabolism to neural invasion, and identify promising therapeutic targets for PDAC.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42017444 · DOI · PMC13335594
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis [5]
- Research article Sphingosine 1-phosphate and cancer [6]
- Research article Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis [7]
- Research article Sphingosine 1-phosphate: Lipid signaling in pathology and therapy [8]
- Research article Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy [9]
- Research article An update on sphingosine-1-phosphate and other sphingolipid mediators [10]
References
- Pei G, Zyla J, He L, Moura-Alves P, Steinle H, Saikali P, et al.. Cellular stress promotes NOD1/2-dependent inflammation via the endogenous metabolite sphingosine-1-phosphate. . 2021. PMID 33942347 · DOI · PMC8246065
- Hering M, Madi A, Sandhoff R, Ma S, Wu J, Mieg A, et al.. Sphinganine recruits TLR4 adaptors in macrophages and promotes inflammation in murine models of sepsis and melanoma. . 2024. PMID 39025856 · DOI · PMC11258287
- Janneh AH, Kassir MF, Dwyer CJ, Chakraborty P, Pierce JS, Flume PA, et al.. Alterations of lipid metabolism provide serologic biomarkers for the detection of asymptomatic versus symptomatic COVID-19 patients. . 2021. PMID 34244584 · DOI · PMC8270895
- Peng W, Cao M, Huang H, Bai S, Liu L, Liang J, et al.. Cancer-Associated Fibroblast-Derived Sphingosine-1-Phosphate Activates a MALL-SDC4 Axis to Facilitate Perineural Invasion in Pancreatic Cancer. . 2026. PMID 42017444 · DOI · PMC13335594
- Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G, et al.. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov. 2010. PMID 21031003 · DOI
- Pyne NJ, Pyne S. Sphingosine 1-phosphate and cancer. Nat Rev Cancer. 2010. PMID 20555359 · DOI
- Chun J, Hartung HP. Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin Neuropharmacol. 2010. PMID 20061941 · DOI · PMC2859693
- Cartier A, Hla T. Sphingosine 1-phosphate: Lipid signaling in pathology and therapy. Science. 2019. PMID 31624181 · DOI · PMC7661103
- Proia RL, Hla T. Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest. 2015. PMID 25831442 · DOI · PMC4409021
- Fyrst H, Saba JD. An update on sphingosine-1-phosphate and other sphingolipid mediators. Nat Chem Biol. 2010. PMID 20559316 · DOI · PMC3001344
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.